The present invention, in some embodiments thereof, relates to image analysis and processing and, more particularly, but not exclusively, to analysis of imaging data pertaining to blood flow.
For human sense and movement, homeostasis and various higher functions such as emotion, memory, language and thinking, there are often control mechanisms for each specific site or region in the brain. Such localization of functions in the brain had been confirmed by observing changes in behavior of patients suffering from regional damage to the brain caused by trauma or cerebral blood vessel impediment, or states of epileptic attack, and by estimating the function of the damaged region.
Brain metabolism and function are attributed to the neurovascular unit. This unit comprises the cerebral circulation, including the pial and intraparenchymal cerebral blood vessels with their extrinsic and intrinsic innervation, perivascular pericytes, astrocytes and surrounding neurons. The regional cerebral blood flow (rCBF) is related to neuronal activity and metabolic demand, also known as “neurovascular coupling”. In addition, the rCBF is autoregulated and can therefore remain constant over a wide range of perfusion pressures. In pathological brain conditions associated with vascular abnormalities (e.g., stroke) and primary neuronal dysfunctions (e.g., epileptic seizure and cortical spreading depression), regulation of the rCBF is often impaired. For example, under subarachnoid hemorrhage and traumatic brain injury, neurovascular coupling may be breached, leading to exacerbation of ischemic neuronal damage.
Until recent years, assessment of the cerebrovascular status in intensive care unit (ICU) patients has been confined to the determination of cerebral perfusion pressure using intracranial pressure measurements. New techniques for cerebrovascular assessments include thermal diffusion flowmetry, which has been used in the ICU owing to the availability of a new generation of intracranial probes. The probe provides regional cerebral blood flow (rCBF) data in absolute units (e.g., ml/100 g/min). Several types of such probes are described, for example, in U.S. Pat. Nos. 4,354,504, 4,677,985 and 5,207,227.
Another technology is transcranial Doppler velocimetry in which instruments are equipped with continuous monitoring probes that measure the velocity of blood flow in large intracranial conductance vessels. This technology is described, for example, in U.S. Pat. Nos. 5,379,770, 6,390,979 and 6,468,219.
An additional technology which is used for measuring CBF is laser Doppler flowmetry which measures the movement of red blood cells within the microcirculation using Doppler shifts undergone by coherent radiation generated by lasers. Typically, a fiberoptic probe structure is placed in contact with the tissue and guides incident light from the laser source to the tissue, as well as back-scattered light from the tissue to a photodetector within a flowmeter instrument. The flowmeter instrument processes the photodetector signal to elaborate a continuous voltage signal versus time which is linearly proportional to the real blood flow. Laser doppler based techniques are described in, e.g., U.S. Pat. Nos. 5,579,774 and 5,916,171.
Also known are various brain tissue imaging techniques such as computer tomography (CT), positron emmision tomography (PET) and magnetic resonance imaging (MRI) which allow diagnosing focal regions by imaging.
A mechanism that that protects the brain from fluctuations in blood chemistry is known as “Blood-Brain Barrier” (BBB). The BBB is a complex structural and functional barrier for the maintenance of the normal environment for nerve cells in the central nervous system. Brain endothelial cells are different from those found in other tissues of the body. In particular, they form complex tight junctions between themselves. Function of the BBB depends on these tight intercellular junctions which, together with other components of the barrier, form a continuous “wall” against the passive movement of many molecules from the blood to the brain. Endothelial cells within the central nervous system (CNS) also display fewer pinocytotic vesicles, which in other tissues allow somewhat unselective transport across the capillary wall. In addition, continuous gaps or channels running through the cells, which would allow unrestrained passage, are absent. Yet, this isolation of the brain from the bloodstream is not complete, since an exchange of nutrients and waste products does exist. The presence of specific transport systems within the capillary endothelial cells assures that the brain receives, in a controlled manner, all of the compounds required for normal growth and function.
The unique biological aspect of the BBB is oftentimes addressed in the context of treatment of CNS disorders. The BBB serves as the main obstacle for the delivery of drugs into the brain by either preventing their entrance or facilitating transport from the brain back to the circulation once they crossed, by drug transport proteins, probably contributing to drug resistance in some cases (e.g., epilepsy). In addition, BBB breakdown has been reported in almost all CNS disorders including brain tumors, ischemic events, tumors, brain tumors, multiple sclerosis and neurodegenerative disorders (e.g., Alzheimer's disease).
In recent years it is recognized that BBB breakdown may lead directly to malfunction of the neurovascular unit and hence to long-lasting changes in neuronal activity, followed by neuronal loss.
Over the years, extensive research has been made in the BBB field. Attempts have made to develop agents capable of crossing the BBB (see, e.g., U.S. Pat. Nos. 4,801,575, 5,004,697, 6,419,949 and 6,294,520), agents which increase BBB permeability (see, e.g., U.S. Pat. Nos. 5,434,137, 5,506,206 and 5,591,715), and various techniques for delivering substances across the BBB (see, e.g., U.S. Pat. Nos. 5,670,477, 5,752,515 and 6,703,381), treating a damaged BBB (see, e.g., U.S. Pat. No. 4,439,451), analyzing the BBB (see, e.g., U.S. Pat. No. 6,574,501), and the like. Numerous attempts have also been made to develop techniques for testing the ability of substances to cross the BBB. To this end see, e.g., U.S. Pat. No. 5,266,480.